The overall objective of this proposal is to carry out a systematic investigation of the pharmacokinetics and pharmacodynamic effects of methadone, LAAM and heroin in the maternal-fetal unit. The study will be divided into two phases. Both phases will be carried out using the chronic pregnant ewe animal model. Phase I will involve the study of the distribution and elimination of the drug and metabolites in the mother and fetus after acute administration. The effects of acute drug administration on maternal and fetal blood gases, heart rate, blood pressure, uterine and umbilical blood flow and substrate uptake by the fetus will be determined. The uptake and release of the drug and metabolites by the fetal brain and their effects on fetal brain function (EEG) and cerebral metabolism will also be studied. Phase II will involve chronic administration of the drug during the third trimester with intermittent blood sampling in order to determine the distribution and accumulation of the drug and metabolites in mother and fetus. The effects of chronic drug administration on uterine and umbilical blood flow, substrate uptake and utilization by the fetus, and the development of fetal brain function will be studied. The effects of chronic drug administration on fetal growth and development will also be evaluated. An understanding of the pharmacokinetics and pharmacodynamic actions of the drug in the maternal-fetal unit may lead to a better understanding of the mechanisms by which these drugs affect fetal growth and development. This proposal also provides the means for formulating a pharmacologic basis for the proper selection of these drugs in the pregnant addict.